Transposable elements (TEs; or transposons) are highly abundant mobile genetic elements that comprise multiple classes and constitute a large fraction of most eukaryotic genomes. The class known as retrotransposons, for example, comprises about 40 and 30 percent of the human and Drosophila genomes, respectively. (Belancio et al., Genome Res. 2008, 18, 343-358; Goodier and Kazazian, Cell 2008, 135, 23-35; 2-5).
The movement and accumulation of TEs has been a major force in shaping the genes and genomes of almost all organisms. (Feschotte and Pritham, Annu. Rev. Genet. 2007, 41, 331-368; Hancks and Kazazian, Curr. Opin. Gen. Dev. 2012, 22, 191-202; Burns and Boeke, Cell 2012, 149, 740-752). This force is not without potential adverse consequences, however: TEs represent a massive reservoir of potential genomic stability and RNA-level toxicity that must also be kept in check. Indeed, many TE appear static and non-functional.
However, at least some TEs are capable of replicating and mobilizing to new positions in the genome—and even immobile TE copies can be expressed. And endogenous transposition itself has been detected in the germline—where TEs have been most extensively investigated (Belancio et al., Genome Res. 2008, 18, 343-358). In addition, somatic transposition events have observed in early embryonic development and during neurogenesis. (Goodier and Kazazian, Cell 2008, 135, 23-35; 2-5; Muotri et al., Nature 2010, 468, 443-446; Baillie et al., Nature 2011, 479, 534-537; Coufal et al., Proc. Natl. Acad. Sci. USA 2011, 108, 20382-20387).
These observations do not, however, address the extent to which TEs are expressed or mobilized in the brain during normal aging—much less the possible functional consequences of such activation. Clarifying these issues may afford new mechanistic insights into aging and related physiological processes. The present invention meets these and other needs in art, providing new tools, along with new diagnostic and therapeutic methods, as disclosed herein.